Genetic Polymorphisms of CYP2D6: Prevalence in Healthy Kurds

(E-pub Ahead of Print)

Author(s): Muslih Abdulkarim Ibrahim* , Zalina Zahari* , Nurfadhlina Musa , Khoo Boon Yin .

Journal Name: Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics)

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Background: Identifying the genetic polymorphisms of drug metabolizing enzyme CYP2D6 is useful in the pharmacogenomics. Unfortunately, until today, the prevalence of the CYP2D6 polymorphisms among Kurds is scarce.

Objective: In this study, we explored the CYP2D6 polymorphisms among Kurds.

Method: Four hundred and fifty-nine unrelated healthy Kurds were recruited for the study. DNA was extracted from whole blood and then was used for genotyped CYP2D6*3, *4, *5, *6, *9, *10, *17, *114 and gene duplication using the nested allele-specific multiplex polymerase chain reaction (PCR).

Results: The most common alleles and genotypes identified were CYP2D6*1 (75.5%), gene duplication (10.0%), *4 (8.6%), *10 (3.4%) and CYP2D6*1/*1 (62.5%), *1/*4 (16.3%), *1/*1xN (8.3%) and *1/*10 (6.3%). Thirty-nine (8.5%) subjects had genotypes that predicted ultrarapid metaboliser (UM) phenotypes, whereas two (0.4%) showed genotypes that predicted intermediate metabolisers (IMs), and four (0.8%) subjects had genotypes that predicted poor metabolism (PMs).

Conclusion: The data add to our knowledge of CYP2D6 alleles, the genotypes and the distributions of predicted phenotypes in Kurds. Majority of the observed variant alleles confer no function and gene duplication. CYP2D6 polymorphisms were found to be very heterogeneous in relations to genotype frequencies. Further study in relation to the evaluation of drug therapy adjustment based on CYP2D6 genotype may help to understand the clinical consequences of CYP2D6 polymorphisms.

Keywords: CYP2D6, pharmacogenetics, polymorphism, Kurds, debrisoquine-4-hydroxylase, CYP2D6 genotype

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(E-pub Ahead of Print)
DOI: 10.2174/1875692117666190416145331

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